Skin Immunization With ALFQ-Adjuvanted SARS-CoV-2-Spike Ferritin Nanoparticles Induces Broad and Durable Immunity in Young and Aged Mice 2259612
The development of next-generation SARS-CoV-2 vaccines with increased humoral and cellular immunogenicity and improved safety, durability, and thermostability is a high-priority goal for global public health. Here, we introduce a next-generation SARS-CoV-2 vaccine candidate. We formulated SARS-CoV-2 spike protein ferritin nanoparticle adjuvanted with Army Liposome Formulation containing QS-21 into dissolvable microneedle patches. We (1) conducted the biophysical characterization of SpFN+ALFQ MNPs to probe their delivery performance and thermostability, (2) assessed the local and systemic innate responses, and (3) evaluated the humoral and cellular responses in systemic and mucosal compartments. SpFN+ALFQ MNP successfully delivered SpFN and ALFQ to the same antigen-presenting cell rich skin microenvironments and maintained its immunogenicity at room temperature for at least a year. SpFN+ALFQ MNP induced a proinflammatory local immune microenvironment (i.e., upregulation of Th1-predominant cytokines and chemokines) without local and systemic reactogenicity. Immunization with SpFN+ALFQ MNP evoked strong humoral and cellular responses in systemic and mucosal compartments, with Th1 bias. SpFN+ALFQ MNP-elicited antibodies were cross-reactive and long-lived (at least 76 weeks) and effectively neutralized many SARS-CoV-2 variants of concern. SpFN+ALFQ MNP-induced systemic and pulmonary antigen-specific polyfunctional CD4+ and CD8+ T-cell responses with robust lytic activity. Importantly, SpFN+ALFQ MNP induced comparable antibody responses in young and aged mice. Together, these unique safety, thermostability, and innate and adaptive immunity characteristics of SpFN+ALFQ MNP provide a strong foundation for the development of rapidly translatable next-generation vaccines leveraging ferritin nanoparticle antigens, ALFQ, and MNPs against SARS-CoV-2 and other emerging pathogens. Department of Defense, National Institutes of Health Vaccines and Immunotherapy (VAC)